The purpose of this research study is to see if a specific type of radiation therapy, called "proton pulsed reduced dose rate" or "PRDR radiotherapy" has any benefits at dose levels and number of fractions thought to be acceptable in earlier research studies. The researchers want to find out what effects (good and bad) PRDR has on people with cancer in the brain called a "recurrent high-grade glioma" meaning that it grows fast, can spread quickly, and it has come back or gotten worse after being treated previously.

Inclusion Criteria:

• Karnofsky performance status ≥ 50

• Histologically-confirmed or radiographic evidence of recurrent / progressive glioma

• Prior treatment with radiotherapy to a minimum dose of 45 Gy

• At least 6 months or greater between completion of prior radiotherapy and enrollment in this study. If prospective participants have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria:

  1. New areas of tumor outside the original radiotherapy fields as determined by the investigator.
  2. Histologic confirmation of tumor through biopsy or resection AND an interval of at least 90 days between completion of radiotherapy and enrollment.
  3. Nuclear medicine imaging, magnetic resonance (MR) spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of enrollment AND an interval of at least 90 days between completion of radiotherapy and enrollment.

• Must have recovered from grade 3+ toxicities of prior therapy and there must be a minimum time of 28 days prior to enrollment from the administration of any investigational agent or prior cytotoxic therapy

• Must not be pregnant (positive pregnancy test) or breastfeeding. Must agree to use of highly effective contraception during radiotherapy treatment and for an additional 6 months. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately.

Highly effective and acceptable forms of contraception are:

• Male condom plus spermicide
• Cap plus spermicide
• Diaphragm plus spermicide
• Copper T
• Progesterone T
• Levonorgestrel-releasing intrauterine system (e.g., Mirena®)
• Implants
• Hormone shot or injection
• Combined pill
• Mini-pill
• Patch

Individuals who meet any of the following criteria will not need contraception:

• Individuals assigned male at birth
• Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for individuals under 50
• Radiation-induced oophorectomy with last menses > 1 year ago
• Chemotherapy-induced menopause with >1 year interval since last menses
• Surgical sterilization (bilateral oophorectomy or hysterectomy)

Exclusion Criteria:

• Two or more courses of prior radiotherapy
• Inability to undergo an MRI with contrast
• Leptomeningeal evidence of recurrent disease
• Multi-focal disease
• Any other condition that may put a participant at higher risk, at the discretion of the investigator.