Inclusion Criteria:
1. 6 years to 21 years\* of age.
2. Lesion number and size:
1. Phase 1a/b only: A single lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor (subsequent to individual Cohort lesion size requirements).
2. Phase 2a only: A single lesion or any number of multiple lesions separated by (less than or equal to) ≤3 cm; each lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor.
3. Diagnosis:
a) Documented recurrent, refractory, or progressive ependymoma or HGG not eligible for resection or no longer receiving standard of care.
i) Phase 2a only: May include patients with recurrent, refractory, or progressive ependymoma or HGG where SOC surgery could be safely delayed four (4) weeks post-infusate.
b) Documented histologically confirmed high-grade glioma \[following 2021 WHO CNS5 glioma nomenclature, e.g., Anaplastic astrocytoma, Anaplastic pleomorphic xanthoastrocytoma (PXA), Anaplastic ganglioglioma, Anaplastic oligodendroglioma, Glioblastoma, Diffuse midline glioma, H3K27M mutant\].
4. Karnofsky Performance Status ≥ 60. For subjects \<16 years of age, Lansky score ≥ 60.
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 (ULN)
6\) Acceptable renal function:
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1. Serum creatinine ≤1.5xULN
7\. Acceptable hematologic status (without hematologic support):
1. ANC ≥1000 cells/uL
2. Platelet count ≥100,000/uL
3. Hemoglobin ≥9.0 g/dL
8\. All subjects of childbearing potential must have a negative serum pregnancy test, and 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\. Life expectancy of at least 2 months.
\*Will consider treatment of subjects up to 25 years of age on a per-patient basis if no other co-morbidities are present that require subspecialty consultation outside of neurosurgical and oncologic care.
Exclusion Criteria:
1. Spinal disease.
2. Infratentorial location of tumor.
3. Involvement of the leptomeninges.
4. Serious intercurrent illness, as determined by the treating physician, which would compromise either patient safety or study outcomes such as:
1. Hypertension (two or more blood pressure readings performed at screening of systolic blood pressure (SBP) or diastolic blood pressure (DBP) above 95th percentile for age) despite optimal treatment.
2. Active medically significant infection unresponsive to antibiotics (e.g., non-healing wound, ulcer), uncontrolled systemic infection, or bone fracture.
3. Clinically significant cardiac arrhythmias.
4. Untreated hypothyroidism.
5. Congestive heart failure.
6. Myocarditis.
7. Inherited bleeding diathesis or coagulopathy with the risk of bleeding.
8. Known active malignancy other than ependymoma or high-grade glioma.
5. Any of the following prior anticancer therapy:
1. Prior treatment with Bevacizumab or other VEGF agents within 12 months prior to study registration.
2. Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site at any time prior to study registration.
3. Standard radiation therapy within 12 weeks prior to study registration.
4. Any systemic therapy within 28 days or 2 half-lives, whichever is longer, prior to study registration (this may include investigational agents, small-molecule kinase inhibitors, non-cytotoxic hormonal therapy, biologic agents, metronomic/protracted low-dose chemotherapy, etc.).
5. Nitrosoureas or mitomycin C within 42 days prior to study registration.
6. Psychiatric illness/social situations that would limit compliance with the study requirements.
7. A tumor located within 1.0cm of a ventricle AND it is determined by the surgeon, PI, and Sponsor to be a risk for drug extravasation to the subarachnoid space if given catheter placement and drug administration.
8. A tumor within 1.5cm of critical structures, including the optic chiasm, optic nerves, or brainstem.
9. Evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan (subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible).
10. Treatment with antiepileptic medications must have a two-week history of a stable dose of antiepileptic without seizures prior to study registration.
11. Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms prior to study registration.
