Inclusion Criteria:

* Age \>= 18 years
* Clear clinical and radiographic evidence of primary high grade glioma (HGG) as judged by the Mayo multidisciplinary neuro-oncology team (World Health Organization \[WHO\] grade III-IV, including glioblastoma) regardless of IDH and MGMT status
* Patients who underwent a previous biopsy confirming high grade glioma are eligible for enrollment to either cohort if a further resection is planned
* Planned neurosurgical resection of tumor
* Judged to not be at risk of significant clinical risk (i.e. herniation) with radiation-induced edema prior to resection
* No prior history of cranial radiotherapy
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
* Negative pregnancy test done =\< 14 days prior to registration, for women of childbearing potential only
* Ability to complete questionnaire(s) by themselves or with assistance
* Provide written informed consent
* Planning to receive adjuvant radiotherapy at enrolling institution
* Willing to provide tissue and/or blood samples for correlative research purposes
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained =\< 14 days prior to registration)
* Platelet count \>= 80,000/mm\^3 (80 x 10\^9/L) (obtained =\< 14 days prior to registration)
* Hemoglobin (Hgb) \>= 9 g/dL (=\< 14 days prior to registration)

Exclusion Criteria:

* Any of the following:

* Pregnant women
* Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception
* Unwillingness to participate in study
* Investigator discretion that enrollment on the study would pose undo harm or risk to the patient
* Non-MRI compatible implanted medical device
* Use of systemic anti-cancer therapy within the previous 3 months
* Medical contraindication to craniotomy and tumor resection
* Pathologic confirmation of grade I-II glioma, brain metastasis, or other brain tumor

* Note: Patients with a history of grade I-II glioma are eligible if they have only received surgery as treatment and now there is concern for transformation to grade III-IV tumor
* Primary spinal cord glioma or primary brainstem glioma
* Residual tumor of excessive volume or eloquent location per investigator discretion
* Patients who are unwilling or unable to comply with study procedures

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/02/2024. Questions regarding updates should be directed to the study team contact.