Inclusion Criteria:
1. At least 18 years of age.
2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
3. Documented LM from any primary solid tumor cancer per EANO-ESMO Clinical Practice Guidelines (Types I or IIA-C).
4. Karnofsky performance status of 70 to 100.
5. Acceptable liver function:
1. Bilirubin ≤ 1.5 times the upper limit of normal.
2. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal for subjects with normal liver.
3. AST (SGOT) and ALT (SGPT) ≤ 5.0 times the upper limit of normal for subjects with liver metastasis.
6. Acceptable renal function:
a. Creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation).
7. Acceptable hematologic functioning (without hematologic support):
1. ANC ≥ 1000 cells μL.
2. Platelet count ≥ 75,000/μL.
3. Hemoglobin ≥ 9.0 g/dL.
8. All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
9. Normal CSF flow and distribution by an accepted CSF flow study (e.g., 111Indium-DTPA or acceptable substitute) before first treatment with the study drug, based on study imaging interpretation and clinical correlation.
10. Corticosteroids are permitted as clinically indicated.
Exclusion Criteria:
1. The subject has not recovered to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study, at time of study registration.
a. Prior AEs due to alopecia, anemia, neutropenia, and lymphopenia are not required to be recovered to Grade ≤1 prior to study registration, assuming other inclusion criteria are satisfied.
2. Contraindications to the placement of an intraventricular catheter (i.e., Ommaya reservoir.)
3. Presence of or need for a Ventriculo-peritoneal or ventriculo-atrial shunt.
4. Females of childbearing potential who are pregnant, breastfeeding, or may possibly be pregnant, without a negative serum pregnancy test (see inclusion criteria).
5. Serious intercurrent illnesses, which could interfere with the planned treatment schedule.
6. Patients who had any therapeutic radiation dose to the whole brain regardless of when the radiation treatment was delivered, except:
1. Prior radiation dose to the spinal cord and/or cauda equina is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been \> 14 days and ≤ 6 months, or was ≤45 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been \> 6 months.
2. Prior stereotactic radiosurgery (SRS) to the brain or partial brain radiotherapy is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been \> 14 days and ≤ 6 months, or was ≤ 45 Gy to the brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been \> 6 months.
7. Prior or concurrent therapy:
a. Intrathecally delivered therapy: i. Concurrent: Concurrent intrathecal therapy. ii. Prior: Intrathecal therapy given less than 14 days before study registration.
b. Systemically delivered therapy: i. Concurrent: Systemically delivered therapy UNLESS LM develops while on systemically delivered therapy AND the systemically delivered therapy is NOT associated with more than grade 1 myelosuppression.
ii. Prior: Systemically delivered therapy given less than 28 days before study registration.
8. Projected survival of less than 60 days.
