Inclusion Criteria:
* Documented informed consent given by the participant. Non-English speaking adults are eligible for participation if they have the capacity to understand and consent to the study procedures
* Age: ≥ 18 years
* Karnofsky Performance Status (KPS) ≥ 70%
* Histologically confirmed glioblastoma or radiographic findings consistent with a high grade glioma
* Newly diagnosed or recurrent tumor
* The patient is planning to undergo a standard-of-care craniotomy for gross total resection of enhancing tumor
* The patient's pre-operative brain MRI shows the presence of mild to moderate cerebral edema, defined as a midline shift of less than 10 mm
* Dose Levels 1-3 participants: If taking more than a total of 6 mg a day of dexamethasone at the time of signing the consent form, it is anticipated by the neurosurgeon that the participant will be able to decrease their dose of dexamethasone to 6 mg daily by 4 days before the surgery (pre-operative Day -4)
* Dose Level 4 participants: If taking more than 1 mg a day of dexamethasone at the time of signing the consent form, it is anticipated by the neurosurgeon that the participant will be able to taper their dose of dexamethasone to 1 mg daily or less by pre-operative Day -4
* The patient is not planning to be in another clinical trial during the study period
* The patient has recovered from any acute toxic effects (except alopecia) to ≤ grade 1 of prior anti-cancer therapy
* No limit to prior number of therapies. The following time periods must have elapsed prior to the start of study treatment: 6 weeks from nitrosourea-containing chemotherapy, 4 weeks from non-nitrosourea-containing cytotoxic chemotherapy (except 23 days from last daily dose of temozolomide taken in a 5 of 28 day regimen, 5 half-lives from last dose of a targeted agent, and 4 weeks from the last dose of bevacizumab). There is no time period requirement for prior radiation therapy
* Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
* Platelets ≥ 100,000/mm\^3
* Hemoglobin ≥ 9g/dL
* Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
* Aspartate aminotransferase (AST) ≤ 1.5 x ULN
* Alanine aminotransferase (ALT) ≤ 1.5 x ULN
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min
* International Normalized Ratio (INR) OR Prothrombin (PT) ≤ 1.5 x ULN
* Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN
* Corrected QT interval (QTc) ≤ 450 ms
* Must have a Fridericia's corrected QT interval (QTcF) ≤ 450 msec calculated with Fridericia formula
* Left ventricular ejection fraction (LVEF) ≥ 50%
* People of childbearing potential who have uteri: negative urine or serum pregnancy test
* Contraception:
* Agreement by participants of childbearing potential or participants who are partners of people with childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy.
Contraception guidance (as per the information included in the informed consent document):
* Acceptable medically effective forms of birth control are:
* Surgical sterilization (tubal ligation or hysterectomy, or vasectomy, as applicable),
* Double-barrier methods (i.e. condoms, diaphragm, cervical cap, or sponge used with spermicidal gel or foam),
* Intrauterine device (IUD) (i.e. Progestin, Copper),
* Hormonal Contraceptives (Birth control patches, implants, pills, rings, or injections)
Exclusion Criteria:
* The patient is taking a medication that is a strong or moderate inducer or inhibitor of major CYP450 isoenzymes and drug transporters, and the patient is not able to stop that medication at least 14 days prior to start of study treatment
* The patient has a risk factor for torsades de pointes, such as structural heart disease (history of myocardial infarction, congestive heart failure, left ventricular hypertrophy), electrolyte abnormalities (hypokalemia, hypomagnesemia), bradycardia or heart blocks, or a family history of Long QT syndrome
* The patient is taking a medication that prolongs the QT/QTc interval and is not able to stop that medication at least 14 days prior to start of study treatment
* The patient is unwilling to stop taking herbal medications prior to the start of study treatment
* The patient is taking a hepatic enzyme-inducing anti-seizure medication within 14 days prior to start of study treatment
* Patient is planning to participate in clinical trial or start a new therapy for their brain tumor during the study period: Day -2 to Day 14
* Patient has not recovered from toxicities of prior therapy (must be grade 1 or less) except alopecia
* Adults who lack the capacity to provide informed consent, including individuals who would require consent from a Legally Authorized Representative (LAR)
* Clinically significant uncontrolled illness
* Active infection requiring antibiotics
* Participants with human immunodeficiency virus (HIV) are excluded due to concerns about inadvertent augmentation of infectious and/or inflammatory activity
* Undergoing treatment for another cancer
* Issues with tolerating oral medication (e.g. inability to swallow, malabsorption issues, ongoing nausea or vomiting)
* Chronic or active viral infection of the CNS
* Participant is pregnant or breastfeeding
* Coagulopathy or bleeding disorder
* Inability to undergo a brain MRI
* Inability to tolerate dexamethasone
* Any other condition that would, in the investigator's judgment, contraindicate participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)