Concurrent Azeliragon With Craniospinal Irradiation

Inclusion Criteria:

* Patient with solid tumor malignancy or high grade glioma with leptomeningeal metastasis established radiographically and/or through cerebrospinal fluid (CSF) cytology
* Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastasis
* Patients with Karnofsky Performance Status of 60 or greater.
* Male or non-pregnant and non-lactating female and ≥ 18 years of age.
* Patients with absolute neutrophil count (ANC) ≥ 1.0 × 109/L, platelet count ≥ 75,000/mm3 (75 × 109/L), and hemoglobin (Hgb) ≥ 8 g/dL. Transfusion or growth factor support is allowed.
* Patients with aspartate aminotransferase (AST) \[serum glutamic-oxaloacetic transaminase(SGOT)\], alanine aminotransferase (ALT) \[serum glutamic-pyruvic transaminase (SGPT)\] ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 x ULN is acceptable, total bilirubin ≤ 1.5 × ULN, and estimated creatinine clearance of \> 30 mL/min (per Cockroft-Gault formula).
* Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

Exclusion Criteria:

* Patient has a life expectancy, per investigator assessment, of less than 2 months.
* Patients unable to complete the English quality of life questionnaires
* Patient with extensive systemic disease and who declined standard systemic treatment options
* Patient who is unable to undergo magnetic resonance imaging (MRI) brain and spine with gadolinium contrast
* Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerance
* Active, uncontrolled bacterial, or fungal infection(s) requiring systemic therapy.
* Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity.
* Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication.
* Patients with a gastrointestinal condition that could interfere with swallowing or absorption.
* Females of childbearing potential who are sexually active or males with female partners of childbearing potential, where either the female or the male is unwilling to use a highly effective method of contraception during the trial and for 6 months after the last administration of study drug.
* Pregnant or lactating women